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Anatomy and Physiology of Hemopoiesis
John Matthews
Queens Hematology
The Bare Essentials
All blood cells originate from pluripotent stem cells which reside in the bone marrow and circulate in the blood
The pluripotent stem cell differentiates (commits) into two lineages in the bone marrow: the myeloid lineage and the lymphoid lineage
The myeloid lineage gives rise to all myeloid cells erythrocytes, granulocytes (neutrophils, eosinophils, basophils), monocytes and platelets
The lymphoid stem cell is generated in the bone marrow: thereafter, development of T and B-cells involves the marrow, thymus, and peripheral lymphoid organs
Hematological neoplasms may affect the pluripotent stem cell or any of its committed progeny
Stem cells may be harvested from the blood or marrow and used to treat patients
Lifespan and production of blood cells
Cell typeApproximate lifespanProduction rate cells/dayProduction rate cells/secProduction rate Kg/yearRed Cells100 days2 x 10112.3 million7.3Neutrophilst 6 hours3 x 1010350,00010.9Platelets7 days1 x 10111.2 million4.6Lymphocytest 10 days1 x 1010116,0003.7Annual total26.5 KgDefinitions
Stem CellPluripotentCommittedMyeloidLymphoidStem cell can self renew and differentiate
Makes myeloid and lymphoid expand include pulmonary macrophages etc
explain pluripotent and committed
Stem Cell Hierarchy
explain that stem cells and progenitor cells not morphologically recognizable
Stem Cell Assay
MiceLiquid cultureSemi-solid mediaStem cells not seen but named by assay technique
Repop whole mouse spleen colonies mix of cell types product of a single cell can take whole colony and repopulate another mouse etc etc
Liquid LTCIC
Semi-solid media nomenclature different colonies eg CFU-GM and others
Stem cells
Lethal dose radiation
Syngeneic marrow
Stem cells
red cell colonies CFU-E
red cell bursts
BFU-E
Stem cells
granulocyte colonies CFU-G
macrophage colonies CFU-M
Stem cells
granulocyte/ macrophage colonies CFU-GM
mixed colonies
CFU-GEMM
Human Hemopoiesis
Points to remember two lineages hierarchy of increasing commitment and differentiation
Recognizable late
Emphasize that marrow stroma is not derived from the HSC
HSC gives all macrophages and dendritic cells eg pulmonary macrophages, Kupffer cells etc
Red marrow
Red marrow
bone trabecula
blood and fat
Red marrow
bone trabecula
blood and fat
Red marrow with sinusoid
66.unknownMarrow cells
red cell precursor
white cell precursor
Control of Hemopoiesis
Eg epo, tpo, scf
Control of Hemopoiesis
Growth Factors e.g. stem cell factorHormones e.g. erythropoietin, thrombopoietin, filgrastimSinusoidal epitheliumAssessment of Hemopoiesis
Blood countReticulocytesMarrow examinationStem Cell Transplant
AllogeneicAutologousGet stem cells from blood or marrow
Infuse intravenously and home
Autologous vs allogeneic
Bone marrow stem cell harvest
Bone marrow stem cell transplant
Bone marrow stem cell transplant
Disease States
Failure of stem cellsNeoplasiaBone marrow biopsy in aplasia
normal
aplastic anemia
Bone marrow aspirate in acute leukemia
normal
acute leukemia
Therapeutic use of Growth Factors
ErythropoietinFilgrastimThrombopoietin analogs